Effect of phenytoin on serum lipoproteins in middle-aged men

We assessed the effect of phenytoin on serum lipids and lipoproteins in a group of 20 male volunteers. Nine of the subjects were healthy, and 11 had coronary heart disease. Their mean age was 44 +/- 7 years. Phenytoin was given at daily doses of 200-350 mg for a period of 4-9 months. Serum total cholesterol increased from 6.9 to 8.1 mmoles/liter (p < 0.001), high-density lipoprotein (HDL) cholesterol from 1.02 to 1.14 mmoles/liter (p < 0.05), low-density lipoprotein cholesterol from 5.0 to 5.9 mmoles/liter (p < 0.05), and total triglycerides from 1.9 to 2.4 mmoles/liter (p < 0.05). The ratio of HDL cholesterol to total cholesterol remained unchanged (14.8 vs. 14.1%). The level of apoprotein A-I increased from 145 to 164 mg/dl (p < 0.001), while A-II remained unchanged. Besides drowsiness, for which 1 patient dropped out, no side effects attributable to phenytoin were seen. As an indication of liver microsomal enzyme induction, serum gamma-glutamyltransferase activity was increased in all subjects during phenytoin treatment. These results cast doubt on the clinical usefulness of phenytoin in treating dyslipidemias.